Metabolism S3 - Energy Production (Carbohydrates and Lipids)

Question 1

The TCA cycle is a central pathway in the catabolism of what compounds?

Answer 1

Sugars, fatty acids, ketone bodies, alcohol and amino acids

Question 2

The TCA cycle occurs where?

Answer 2

Mitochondria

Question 3

Is the TCA cycle oxidative or reductive?

Answer 3

Oxidative

Question 4

What does the TCA pathway require to function?

Answer 4

AcetylCoA, NAD+, FAD and oxaloacetate

Question 5

What is the main function of the TCA cycle?

Answer 5

Break the C-C bond in acetate (as acetylCoA) and oxidise the C atoms to CO2

Question 6

In the TCA cycle what is the involvement of H+ and e-?

Answer 6

Removed from acetate and transferred to NAD+ and FAD+

Question 7

Can the TCA cycle function in anaerobic conditions?

Answer 7

Nope

Question 8

Per molecule of glucose, what does the TCA cycle produce?

Answer 8

2 ATP

2 FAD2H

6NADH

4 CO2

Question 9

Describe the chemical ‘strategy’ of the TCA cycle.

Answer 9

Produce intermediates (C5 tricarboxylic acids and keto acids) that readily lose CO2 producing C4 acids that are interconvertible.

Question 10

What are the anabolic functions of the TCA cycle?

Answer 10

C5 and C4 intermediates used in non-essential amino acid synthesis

C4 intermediates used for the synthesis of haem and glucose

C6 intermediates used for synthesis of fatty acids

Question 11

What is the main method of TCA cycle regulation?

Answer 11

One Irreversible step is catalysed by isocitrate dehydrogenase

This enzyme allosterically controlled by ADP/ATP and NAD+/NADH ratios

ADP activates (low energy signal)

NADH inhibits (high energy signal)

Question 12

Give an equation for the complete oxidation of glucose and the overall release of energy

Answer 12

C6H12O6 + 6 O2 —> 6 CO2 + 6 H2O

2870kJ/mol

Question 13

by the end of the TCA cycle what has happened to glucose’s bonds and bond energy?

Answer 13

All C-C bonds broken

All C atoms oxidised to CO2

All C-H bonds broken and H+/e- transferred to NAD+ and FAD

All energy has gone into ATP/GTP formation

Chemical bond energy of the e- is in NADH or FAD2H form.

Question 14

How much energy is released from the oxidation of NADH and FAD2H?

Answer 14

NADH = 220kJ/mol

FAD2H = 152kJmol

Question 15

What is the energy from the oxidation of NADH and FAD2H used for?

Answer 15

Oxidative phosphorylation

Question 16

Give a brief description of electron transport

Answer 16

Electrons from NADH and FAD2H transferred through a series of carrier molecules in the inner mitochondrial membrane to molecular oxygen, releasing free energy

Question 17

The free energy released from electron transport drives what process?

Answer 17

ATP synthesis

Question 18

how many electron transfer complexes are their?

Answer 18

A series of 4

Question 19

3 of the electron transport complexes have another function, what is this?

Answer 19

They act as proton translocation complexes (proton pumps)

Question 20

how is an electrochemical gradient set up across the inner mitochondrial membrane?

Answer 20

Protons moved into the inter membrane space across the impermeable inner mitochondrial membrane of the mitochondrion using electrochemical energy generated from electron trnasport

Question 21

how and why do NADH and FAD2H utilise the protons pump differently

Answer 21

NADH releases more energy, so uses all three proton pumps while FAD2H only uses 2

Question 22

What is the role of oxygen in the electron transport chains?

Answer 22

final electron acceptor

Question 23

How much energy is required to produce one ATP molecule via oxidative phosphorylation

Answer 23

31kJ/mol

Question 24

How is the proton gradient across the inner mitochondrial membrane used in ATP synthesis?

Answer 24

Protons can only flow through ATP synthase complexes, this produces ATP from ADP and Pi.

Question 25

How many moles of ATP produced per mole of NADH and FAD2H

Answer 25

NADH = 2.5 FAD2H = 1.5

Question 26

electron transport and ATP synthesis are highly coupled, when ATP concentration is high, what happens to these processes?

Answer 26

ATP synthesis stops due to lack of substrate This prevents H+ transport back into matrix H+ concentration continues to increase in intermembrane space until reaching a level that prevents further buildup of H+ In the absence of proton pumping, electron transport stops.

Question 27

What substances can increase permeability of the inner mitochondrial membrane to protons and what is this effect called?

Answer 27

dinitrocresol, dinitrophenol uncoupling

Question 28

what is proton leak?

Answer 28

protons crossing inner mitochondrial membrane into the matrix without passing through the ATP synthase complex

Question 29

how is pmf dissipated when proton leak occurs? What proportion of energy is leaked and under what curcumstances might this proportion increase?

Answer 29

As heat. Normally 20-25% of Basal metabolic rate dissipated as heat, increases when uncoupling occurs

Question 30

What is the purpose of uncoupling proteins?

Answer 30

Uncouple electron transport and ATP synthesis to produce heat

Question 31

What are the three uncoupling proteins?

Answer 31

UCP1 (Thermogenin) UCP2 UCP3

Question 32

What is the function of Thermogenin and where is it found?

Answer 32

Non-shivering thermogensis enabling mammals to survive the cold Expressed in brown adipose tissue

Question 33

Where is UCP2 found and what diseases is it linked to?

Answer 33

Widely distributed Heart failure, diabetes, obesity, metabolic syndrome

Question 34

Where is UCP3 found and what are its functions?

Answer 34

Found in skeletal muscle, brown adipose tissue and the heart. Uncoupling of electron transport Appears to be involved in fatty acid metabolism and protecting against reactive oxygen species damage.

Question 35

what are noradrenaline's effects on metabolism?

Answer 35

Stimulates lipolysis and hence more NADH and FAD2H are produced Activates UCP1 Hence higher levels of pmf dissipated as heat

Question 36

What are the differences between substrate level and oxidative phosphorylation

Answer 36

Oxidative requires membrane associated proteins, substrate level requires soluble enzymes In oxidative couple occurs indirectly through creation and utilisation of pmf, in substrate level energy coupling occurs directly through phosphoryl group transfer Oxidative cannot occur without oxygen, substrate level can occur to limited extent anaerobically Oxidative is a major process in high energy cells, substrate level is a minor process in high energy cells

Question 37

What are the general features of a lipid?

Answer 37

Hydrophobic Most contain CHO (phospholipids contain P and N) More reduced than carbohydrates

Question 38

What are the three major classes of lipid?

Answer 38

Fatty acid derivatives Hydroxy-methyl-glutaric acid derivatives Fat soluble vitamins

Question 39

What types of fatty acid derivatives are found in the body and what are their functions?

Answer 39

Fatty acids - Fuel molecules Triacylglycerols - Fuel storage and insulation Phospholipids - Components of plasma membranes and plasma lipoproteins Eicosanoids - Local mediators/signalling molecules

Question 40

What types of Hydroxy-methyl-glutaric acid derivatives are found in the body and what are their functions?

Answer 40

Ketone bodies - Water soluble fuel molecules Cholesterol - Membranes and steroid hormone synthesis Cholesterol esters - Cholesterol storage Bile acids and salts - Lipid digestion

Question 41

How are triacylglycerols broken down in the small intestine and what are the products of breakdown?

Answer 41

Pancreatic lipase in a complex process requiring colipase and bile salts Releases glycerol and fatty acids

Question 42

Where is glycerol metabolised?

Answer 42

Liver

Question 43

Why are some polyunsaturated fatty acids required in the diet? Give an example of a required polyunsaturate and it's use

Answer 43

Cannot be synthesised by the body Arachidonic acid - Starting point of eicosanoid synthesis

Question 44

What are the three ketone bodies produced by the body?

Answer 44

Acetoacetate Acetone - formed from spontaneous decarboxylation of above, not intentionally formed B-hydroxybutyrate

Question 45

Where are ketone bodies synthesised and what from?

Answer 45

Liver AcetylCoA

Question 46

What is the normal level of ketone bodies in the blood and what could be responsible for this rising?

Answer 46

\<1mM is normal This can increase during starvation to 2-10mM = Physiological ketosis 10mM = Pathological Ketosis, caused by type 1 diabetes

Question 47

What are the basic properties of ketone bodies and what are clinical consequences of these properties?

Answer 47

Water soluble - allows excretion in urine (ketonuria) and high plasma concentration Strong organic acids - In high concentration can cause ketoacidosis

Question 48

How is acetone useful in diagnosis of type 1 diabetes

Answer 48

Acetone is volatile so can be excreted through the lungs. There is a strong smell of acetone on the breath of untreated type 1 diabetes patients

Question 49

During ketone body synthesis what ratio controls what key enzyme?

Answer 49

Insulin/glucagon ratio Controls Hydroxy-methyl-glutaryl CoA (HMG-CoA) Lyase/reductase enzymes

Question 50

How do changes in the Insulin/glucagon ratio affect ketone synthesis?

Answer 50

Reduction in insulin and increase in glucagon stimulates HMG-CoA lyase and hence increased levels of ketone bodies produced Vice versa.

Question 51

What does the synthesis of ketone bodies require? (substrate and conditions)

Answer 51

Fatty acids available for oxidation (excess lipolysis) Plasma insulin/glucagon ration to be low, normally due to fall in plasma insulin

Question 52

How and where are ketone bodies used and how does plasma concentration affect their use?

Answer 52

As fuel molecules in all mitochondria containing cells including the nervous system Converted to AcetylCoA and used in TCA cycle Rate of use proportional to plasma concentration

Question 53

What is Acetyl CoA produced by?

Answer 53

Metabolism of: Fatty acids Sugars Alcohol Certain Amino acids

Question 54

How and where is AcetylCoA utilised?

Answer 54

Oxidised in TCA cycle (mitochondria) Important intermediate in lipid biosynthesis (the major site of which is the liver, some in adipose tissue)